ID PFKB_MYCTU Reviewed; 339 AA. AC P9WID3; L0T8F1; O86352; Q7D7L4; DT 16-APR-2014, integrated into UniProtKB/Swiss-Prot. DT 16-APR-2014, sequence version 1. DT 01-APR-2015, entry version 11. DE RecName: Full=Putative ATP-dependent 6-phosphofructokinase isozyme 2; DE Short=ATP-PFK 2; DE Short=Phosphofructokinase 2; DE EC=2.7.1.11; DE AltName: Full=Phosphohexokinase 2; GN Name=pfkB; OrderedLocusNames=Rv2029c; OS Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv). OC Bacteria; Actinobacteria; Actinobacteridae; Actinomycetales; OC Corynebacterineae; Mycobacteriaceae; Mycobacterium; OC Mycobacterium tuberculosis complex. OX NCBI_TaxID=83332; RN [1] RP NUCLEOTIDE SEQUENCE [LARGE SCALE GENOMIC DNA]. RC STRAIN=ATCC 25618 / H37Rv; RX PubMed=9634230; DOI=10.1038/31159; RA Cole S.T., Brosch R., Parkhill J., Garnier T., Churcher C.M., RA Harris D.E., Gordon S.V., Eiglmeier K., Gas S., Barry C.E. III, RA Tekaia F., Badcock K., Basham D., Brown D., Chillingworth T., RA Connor R., Davies R.M., Devlin K., Feltwell T., Gentles S., Hamlin N., RA Holroyd S., Hornsby T., Jagels K., Krogh A., McLean J., Moule S., RA Murphy L.D., Oliver S., Osborne J., Quail M.A., Rajandream M.A., RA Rogers J., Rutter S., Seeger K., Skelton S., Squares S., Squares R., RA Sulston J.E., Taylor K., Whitehead S., Barrell B.G.; RT "Deciphering the biology of Mycobacterium tuberculosis from the RT complete genome sequence."; RL Nature 393:537-544(1998). RN [2] RP INDUCTION BY HYPOXIA. RC STRAIN=ATCC 25618 / H37Rv; RX PubMed=11416222; DOI=10.1073/pnas.121172498; RA Sherman D.R., Voskuil M., Schnappinger D., Liao R., Harrell M.I., RA Schoolnik G.K.; RT "Regulation of the Mycobacterium tuberculosis hypoxic response gene RT encoding alpha -crystallin."; RL Proc. Natl. Acad. Sci. U.S.A. 98:7534-7539(2001). RN [3] RP INDUCTION BY NITRIC OXIDE (NO) AND BY HYPOXIA, AND DORMANCY REGULON. RC STRAIN=ATCC 25618 / H37Rv; RX PubMed=12953092; DOI=10.1084/jem.20030205; RA Voskuil M.I., Schnappinger D., Visconti K.C., Harrell M.I., RA Dolganov G.M., Sherman D.R., Schoolnik G.K.; RT "Inhibition of respiration by nitric oxide induces a Mycobacterium RT tuberculosis dormancy program."; RL J. Exp. Med. 198:705-713(2003). RN [4] RP BIOTECHNOLOGY. RX PubMed=16931093; DOI=10.1016/j.micinf.2006.03.018; RA Leyten E.M., Lin M.Y., Franken K.L., Friggen A.H., Prins C., RA van Meijgaarden K.E., Voskuil M.I., Weldingh K., Andersen P., RA Schoolnik G.K., Arend S.M., Ottenhoff T.H., Klein M.R.; RT "Human T-cell responses to 25 novel antigens encoded by genes of the RT dormancy regulon of Mycobacterium tuberculosis."; RL Microbes Infect. 8:2052-2060(2006). RN [5] RP IDENTIFICATION AS A DRUG TARGET [LARGE SCALE ANALYSIS]. RX PubMed=19099550; DOI=10.1186/1752-0509-2-109; RA Raman K., Yeturu K., Chandra N.; RT "targetTB: a target identification pipeline for Mycobacterium RT tuberculosis through an interactome, reactome and genome-scale RT structural analysis."; RL BMC Syst. Biol. 2:109-109(2008). RN [6] RP INDUCTION BY CARBON MONOXIDE (CO). RC STRAIN=ATCC 35801 / TMC 107 / Erdman; RX PubMed=18474359; DOI=10.1016/j.chom.2008.03.007; RA Shiloh M.U., Manzanillo P., Cox J.S.; RT "Mycobacterium tuberculosis senses host-derived carbon monoxide during RT macrophage infection."; RL Cell Host Microbe 3:323-330(2008). RN [7] RP INDUCTION BY CARBON MONOXIDE (CO), AND DORMANCY REGULON. RC STRAIN=ATCC 25618 / H37Rv; RX PubMed=18400743; DOI=10.1074/jbc.M802274200; RA Kumar A., Deshane J.S., Crossman D.K., Bolisetty S., Yan B.S., RA Kramnik I., Agarwal A., Steyn A.J.; RT "Heme oxygenase-1-derived carbon monoxide induces the Mycobacterium RT tuberculosis dormancy regulon."; RL J. Biol. Chem. 283:18032-18039(2008). RN [8] RP PUPYLATION AT LYS-283, AND IDENTIFICATION BY MASS SPECTROMETRY. RC STRAIN=ATCC 25618 / H37Rv; RX PubMed=20066036; DOI=10.1371/journal.pone.0008589; RA Festa R.A., McAllister F., Pearce M.J., Mintseris J., Burns K.E., RA Gygi S.P., Darwin K.H.; RT "Prokayrotic ubiquitin-like protein (Pup) proteome of Mycobacterium RT tuberculosis."; RL PLoS ONE 5:E8589-E8589(2010). RN [9] RP ACETYLATION [LARGE SCALE ANALYSIS] AT THR-2, IDENTIFICATION BY MASS RP SPECTROMETRY [LARGE SCALE ANALYSIS], AND CLEAVAGE OF INITIATOR RP METHIONINE [LARGE SCALE ANALYSIS]. RC STRAIN=ATCC 25618 / H37Rv; RX PubMed=21969609; DOI=10.1074/mcp.M111.011627; RA Kelkar D.S., Kumar D., Kumar P., Balakrishnan L., Muthusamy B., RA Yadav A.K., Shrivastava P., Marimuthu A., Anand S., Sundaram H., RA Kingsbury R., Harsha H.C., Nair B., Prasad T.S., Chauhan D.S., RA Katoch K., Katoch V.M., Kumar P., Chaerkady R., Ramachandran S., RA Dash D., Pandey A.; RT "Proteogenomic analysis of Mycobacterium tuberculosis by high RT resolution mass spectrometry."; RL Mol. Cell. Proteomics 10:M111.011627-M111.011627(2011). CC -!- FUNCTION: Catalyzes the phosphorylation of D-fructose 6-phosphate CC to fructose 1,6-bisphosphate by ATP, the first committing step of CC glycolysis. {ECO:0000250}. CC -!- CATALYTIC ACTIVITY: ATP + D-fructose 6-phosphate = ADP + D- CC fructose 1,6-bisphosphate. CC -!- COFACTOR: CC Name=Mg(2+); Xref=ChEBI:CHEBI:18420; Evidence={ECO:0000250}; CC -!- ENZYME REGULATION: Allosterically inhibited by ATP. {ECO:0000250}. CC -!- PATHWAY: Carbohydrate degradation; glycolysis; D-glyceraldehyde 3- CC phosphate and glycerone phosphate from D-glucose: step 3/4. CC -!- SUBUNIT: Homodimer. {ECO:0000250}. CC -!- INDUCTION: A member of the dormancy regulon. Induced in response CC to reduced oxygen tension (hypoxia), low levels of nitric oxide CC (NO) and carbon monoxide (CO). It is hoped that this regulon will CC give insight into the latent, or dormant phase of infection. CC {ECO:0000269|PubMed:11416222, ECO:0000269|PubMed:12953092, CC ECO:0000269|PubMed:18400743, ECO:0000269|PubMed:18474359}. CC -!- BIOTECHNOLOGY: Has strong T-cell and IFN-gamma inducing capacity CC in human tuberculin skin test positive patients, indicating this CC might be a good vaccine candidate. {ECO:0000269|PubMed:16931093}. CC -!- MISCELLANEOUS: Was identified as a high-confidence drug target. CC -!- SIMILARITY: Belongs to the carbohydrate kinase PfkB family. CC {ECO:0000305}. CC --------------------------------------------------------------------------- CC Copyrighted by the UniProt Consortium, see https://www.uniprot.org/terms CC Distributed under the Creative Commons Attribution (CC BY 4.0) License CC --------------------------------------------------------------------------- DR EMBL; AL123456; CCP44802.1; -; Genomic_DNA. DR PIR; D70942; D70942. DR RefSeq; NP_216545.1; NC_000962.3. DR RefSeq; YP_006515441.1; NC_018143.2. DR ProteinModelPortal; P9WID3; -. DR SMR; P9WID3; 13-313. DR EnsemblBacteria; CCP44802; CCP44802; Rv2029c. DR GeneID; 887491; -. DR KEGG; mtu:Rv2029c; -. DR KEGG; mtv:RVBD_2029c; -. DR TubercuList; Rv2029c; -. DR KO; K16370; -. DR OMA; DIAYQLD; -. DR PhylomeDB; P9WID3; -. DR UniPathway; UPA00109; UER00182. DR Proteomes; UP000001584; Chromosome. DR GO; GO:0003872; F:6-phosphofructokinase activity; IEA:UniProtKB-EC. DR GO; GO:0005524; F:ATP binding; IEA:UniProtKB-KW. DR GO; GO:0046872; F:metal ion binding; IEA:UniProtKB-KW. DR GO; GO:0006096; P:glycolytic process; IEA:UniProtKB-UniPathway. DR Gene3D; 3.40.1190.20; -; 1. DR InterPro; IPR002173; Carboh/pur_kinase_PfkB_CS. DR InterPro; IPR011611; PfkB_dom. DR InterPro; IPR029056; Ribokinase-like. DR InterPro; IPR017583; Tagatose/fructose_Pkinase. DR Pfam; PF00294; PfkB; 1. DR PIRSF; PIRSF000535; 1PFK/6PFK/LacC; 1. DR SUPFAM; SSF53613; SSF53613; 1. DR TIGRFAMs; TIGR03168; 1-PFK; 1. DR PROSITE; PS00583; PFKB_KINASES_1; 1. PE 1: Evidence at protein level; KW Acetylation; ATP-binding; Complete proteome; Glycolysis; KW Isopeptide bond; Kinase; Magnesium; Metal-binding; Nucleotide-binding; KW Reference proteome; Transferase; Ubl conjugation. FT INIT_MET 1 1 Removed. {ECO:0000269|PubMed:21969609}. FT CHAIN 2 339 Putative ATP-dependent 6- FT phosphofructokinase isozyme 2. FT /FTId=PRO_0000392912. FT NP_BIND 194 196 ATP. {ECO:0000250}. FT NP_BIND 233 238 ATP. {ECO:0000250}. FT REGION 22 24 Substrate binding. {ECO:0000250}. FT REGION 37 39 Substrate binding. {ECO:0000250}. FT REGION 49 53 Substrate binding. {ECO:0000250}. FT REGION 100 102 Substrate binding. {ECO:0000250}. FT REGION 196 198 Allosteric inhibitor ATP binding. FT {ECO:0000250}. FT ACT_SITE 265 265 {ECO:0000250}. FT METAL 199 199 Magnesium; catalytic. {ECO:0000250}. FT METAL 259 259 Potassium; via carbonyl oxygen. FT {ECO:0000250}. FT METAL 261 261 Potassium; via carbonyl oxygen. FT {ECO:0000250}. FT METAL 295 295 Potassium; via carbonyl oxygen. FT {ECO:0000250}. FT METAL 298 298 Potassium; via carbonyl oxygen. FT {ECO:0000250}. FT METAL 300 300 Potassium; via carbonyl oxygen. FT {ECO:0000250}. FT METAL 302 302 Potassium; via carbonyl oxygen. FT {ECO:0000250}. FT BINDING 37 37 Allosteric inhibitor ATP; shared with FT dimeric partner. {ECO:0000250}. FT BINDING 37 37 ATP; shared with dimeric partner. FT {ECO:0000250}. FT BINDING 150 150 Substrate. {ECO:0000250}. FT BINDING 265 265 Substrate. {ECO:0000250}. FT MOD_RES 2 2 N-acetylthreonine. FT {ECO:0000269|PubMed:21969609}. FT CROSSLNK 283 283 Isoglutamyl lysine isopeptide (Lys-Gln) FT (interchain with Q-Cter in protein Pup). FT {ECO:0000269|PubMed:20066036}. SQ SEQUENCE 339 AA; 35401 MW; D773E363FF73DADD CRC64; MTEPAAWDEG KPRIITLTMN PALDITTSVD VVRPTEKMRC GAPRYDPGGG GINVARIVHV LGGCSTALFP AGGSTGSLLM ALLGDAGVPF RVIPIAASTR ESFTVNESRT AKQYRFVLPG PSLTVAEQEQ CLDELRGAAA SAAFVVASGS LPPGVAADYY QRVADICRRS STPLILDTSG GGLQHISSGV FLLKASVREL RECVGSELLT EPEQLAAAHE LIDRGRAEVV VVSLGSQGAL LATRHASHRF SSIPMTAVSG VGAGDAMVAA ITVGLSRGWS LIKSVRLGNA AGAAMLLTPG TAACNRDDVE RFFELAAEPT EVGQDQYVWH PIVNPEASP //